The invention described herein was made by an employee of the United States Government and others who have assigned all of their right title and interest in and to the invention which may be manufactured and used by or for the Government for Government purposes without the payment of any royalties thereon or therefor.
1. Field of the Invention
The invention relates to an apparatus and method for using atomic oxygen to remove biologically active organic contaminants from the surface of surgical implants and other biomedical devices. More particularly, the invention relates to an apparatus and method for using an atomic oxygen plasma to remove non-living, but biologically active organic contaminants, including endotoxin contaminants, from the surface of surgical implants and other biomedical devices, and the containers used for storing and transporting them, to produce a biologically clean device and container. The process also includes hermetically sealing the device in the container, in-situ in the plasma chamber to form a hermetically sealed package, which may then be gamma ray sterilized for storage and transport.
2. Background of the Invention
It is imperative that surgical implants and other biomedical devices used in or which come into contact with living tissue in a live mammalian or other host body, be free of biologically active organic contaminants, such as endotoxin materials which cause an inflammatory reaction in the host body. The inflammatory reaction can lead to failure of the implant or device to function properly. For example, with surgical implants such as artificial hip joints, heart valves and the like, despite substantial research efforts there is still at the present time a significant failure rate of implants in the human body. This can be due to the inflammation of the surrounding living tissue which grows onto and adheres to all or part of the surface of the device. Inflammation is believed to be due to the presence of endotoxins or other biologically active surface contaminants that are difficult to remove. Various plasmas and chemical treatments have been reported for sterilization, but not for endotoxin removal. Examples of some of the plasma treatments disclosed for sterilization may be found in, for example, U.S. Pat. Nos. 3,948,601; 5,656,238; 5,482,684; 5,163,458 and 5,087,418. Methods for removal of such endotoxins invariably relate to chemical cleaning methods. Even if such a device is successively sterilized, certain endotoxins such as cellular material comprising lipopolysaccharides are typically not removed from the surface of the device. Endotoxins consisting of cellular material, and particularly lipopolysaccharides, have been found to be inflammatory and resistant to removal even after multiple, sequential alcohol/alkali baths followed by acid baths, followed by washing and rinsing. Such multiple baths at elevated temperatures on the order of at least 220xc2x0 C. for four or more hours are the only known methods which have successively removed cellular endotoxins. While high temperatures on the order of about 400xc2x0 C. may thermally decompose biologically active organic contaminants, including endotoxins, such high temperatures may impair the fatigue life of metal implants and will destroy most plastic implants, such as an acetabular cup used in hip implants. Multiple acid and alkali baths degrade polymeric materials, as well as some metal implant materials, and temperatures over about 100xc2x0 C. will damage many polymeric materials. Further, such methods have not been proven to remove all biologically active contaminants from the surface of implants. Therefore, it would be an improvement to the art if endotoxins, including cellular material comprising lipopolysaccharides, could be removed from the surface of both a biomedical device and a container for storing and transporting the device prior to use, without having to resort to harsh, and materials damaging, chemical and heat treatments.
The invention relates to a low pressure and temperature process which comprises (a) using an atomic oxygen plasma to remove non-living, but biologically active organic contaminants, including endotoxins, from the surface of (i) surgical implants and other biomedical devices, and (ii) containers for storing and transporting them, to produce bioclean devices and containers, and (b) hermetically sealing the device in the container, and to an apparatus useful in the process. Hermetically sealing the device in the container produces a package containing a bioclean device, which may then be sterilized in-situ in the sealed container with gamma radiation. The plasma is generated in a hermetically sealed plasma chamber. By bioclean in the context of the invention is meant that those surfaces of a biomedical device which will come into contact with living tissue in a host body or elsewhere (hereinafter xe2x80x9cbiosurfacesxe2x80x9d) and those surfaces of its container which will come into contact with such biosurfaces during the cleaning and sealing (hereinafter xe2x80x9ccontact surfacesxe2x80x9d), are free of biologically active organic contaminants comprising endotoxins, such as cellular material and lipopolysaccharides, as a result of being processed according to the practice of the invention. Thus, the process of the invention biologically cleans both those surfaces of the biomedical device that will come into contact with living tissue in a host body or elsewhere and those surfaces (e.g., the interior surfaces) of the container or package which contact the biosurfaces during the cleaning and sealing. In the process of the invention, the entire surface of an implant, such as a hip implant, is biocleaned by the oxygen plasma. This is achieved by means in the plasma chamber, which manipulates either, or both and preferably both, the device and container during the biocleaning. Thus, both the biosurfaces of the device and the contact surfaces of the container are simultaneously biocleaned in the same plasma chamber. Exposing the sealed package to gamma radiation sufficient to sterilize the biosurfaces of the bioclean device, also sterilizes the interior contact surfaces of the sealed container. After the biocleaning, the device is preferably hermetically sealed in its container in the same chamber in which the biocleaning was conducted, a portion of which comprises the plasma space containing the plasma that achieves the biocleaning, and another portion of which contains means for the manipulation and sealing. In a further embodiment, during biocleaning of the device and container, the atomic oxygen generated by the plasma flows through the chamber and also biocleans the interior of the chamber and at least those surfaces of the manipulation and sealing means located in the chamber, that come into contact with both the biosurfaces and contact surfaces during the process. In a still further embodiment, which is a preferred embodiment, at least one precalibrated witness indicator or coupon is placed in the plasma during the biocleaning of the device and container, to provide preferably a readily discernable visual indication, of whether or not the device and container have been in contact with the atomic oxygen for a time sufficient to achieve the desired biocleaning. This is explained in detail below. By low pressure is meant less than about 500 millitorr and preferably from about 0.1 to 300 millitorr, and by low temperature is meant less than 100xc2x0 C., preferably less than 75xc2x0 C. and more preferably no greater than 60xc2x0 C. The process of the invention is in contrast to prior art processes, which usually leave difficult to remove endotoxins, such as lipopolysaccharides and which do not disclose manipulating the device and container during the biocleaning in the sealed atomic oxygen chamber, so that all biosurfaces and contact surfaces are biocleaned prior to sealing.
An apparatus useful in the practice of the invention broadly comprises a hermetically sealable chamber containing (i) means for generating an atomic oxygen plasma in the chamber and (ii) means for manipulating the biomedical device and its container in the chamber. It will also comprise means for introducing oxygen or a gas comprising oxygen through the chamber at a controlled flow rate, means for evacuating the chamber to the desired subatmospheric pressure and means for inserting and removing the device and container from the chamber. The chamber will preferably also contain means for inserting the biocleaned device into the biocleaned container means, means for closing the container over the device prior to sealing and means for sealing the closed container containing the device, following the atomic oxygen cleaning. The means for generating the atomic oxygen plasma may simply be a pair of opposing and spaced-apart flat plates which comprise a pair of electrodes electrically connected to a suitable high voltage source, with the space between the electrodes defining the region in which the plasma exists, and in which cleaning of the device and container is achieved. A high voltage radio frequency (RF) source, which provides a high voltage RF to the electrodes, is typically located outside the chamber.
Thus, in a broad sense and in one embodiment, the invention relates to a process for biocleaning (i) the biosurfaces of a biomedical device and (ii) at least the contact surfaces of an open, but closeable and hermetically sealable container means for the device, wherein both said biosurfaces and contact surfaces are contacted with atomic oxygen at low temperature and subatmospheric pressure, in a hermetically sealed chamber, and wherein said atomic oxygen is produced by a plasma. In a more specific sense the process comprises biocleaning (i) the biosurfaces of a biomedical device containing non-living, biologically active organic material, including endotoxins and (ii) at least the contact surfaces of an open, but closeable and hermetically sealable container means for the device, with atomic oxygen at low pressure and temperature in a hermetically sealed chamber, for a time sufficient to remove the biologically active organic material, including endotoxins, from these surfaces by oxidation, followed by closing the biocleaned container means over the biocleaned device and then hermetically sealing the container means in the chamber, wherein the device is manipulated during the biocleaning, to insure that all of the biosurfaces and contact surfaces have been biocleaned. This thus forms a hermetically sealed package containing a bioclean device enclosed within, in which the contact surfaces of the container are themselves bioclean. The hermetically sealed package is then preferably exposed to gamma radiation to sterilize the bioclean biosurfaces of the device and the bioclean container contact surfaces inside the container. The device remains bioclean and sterile inside the container. The container means is fabricated of material that is not permeable to biologically active material and will typically comprise a polymeric material which can be sealed to itself by heat, ultrasonics or adhesive means. In a preferred embodiment the container means is fabricated, in clamshell fashion, as a unitary body comprising two halves joined together at a common hinge means which, after the biocleaning is achieved, are hermetically sealed to each other to form a package containing the biocleaned device, and preferably also the witness coupon. A container means fabricated of a resilient thermoplastic has been found to be useful in this embodiment.